Amyotrophic lateral sclerosis (hereinafter abbreviated as "ALS") is a relentlessly progressive disease of the nervous system in the course of which the motor nerves, which carry orders for each body movement from the brain to the muscles, are destroyed. Lacking these instructions, the muscles waste away. Walking, speaking and finally breathing become impossible. Throughout the degeneration process, the victim's intellect remains clear, i.e. healthy, active minds find themselves trapped in increasingly useless, dying bodies. Death follows within an average of five years from the onset of symptoms. The cause of this disease is unknown, and up to now it has been impossible to cure ALS or to achieve clinical benefit for more than a few days.
It now surprisingly has been found that administration of dipeptide derivatives of the formula ##STR3## wherein
R.sub.1 represents a hydrogen atom, an alkyl group containing one to six carbon atoms, a cyclohexyl group or a benzyl group,
Z is one of the following groups (attached to the CO-group in the ring by the valence marked with an asterisk) ##STR4## wherein if Z represents the group (a), R.sub.2 and R.sub.3 together represent an additional bond between the carbon atoms to which R.sub.2 and R.sub.3 are attached, or if Z represents the group (b), R.sub.2 is a hydrogen atom,
R.sub.4 and R.sub.5 may be the same or different and each represents hydrogen or an alkyl group containing one to three carbon atoms and wherein R.sub.5 also may represent a phenyl group, and
R.sub.6 represents a hydrogen atom or a methyl group in anhydrous or hydrated forms and pharmaceutically acceptable salts of these compounds with acids preferably in form of suitable pharmaceutical compositions can cause remarkable improvements in the clinical symptoms of ALS patients lasting for up to several weeks after medication ended.
The compounds of formula I (and hydrates and acid addition salts thereof) and their preparation have been described, e.g., by Schwertner et al in "Structure and Activity of Natural Peptides" (Editors W. Voelter and G. Weitzel) Walter de Gruyter-Verlag, Berlin--New York 1981, pp. 397-415, in U.S. Pat. No. 4,045,556 and British Pat. No. 1,564,078, and elsewhere. The disclosures of these documents are hereby incorporated herein by reference.
In the cited publications it has been found that the compounds of formula I on parenteral or oral administration provide long-lasting central nervous system stimulating effects and that the toxicity of the compounds is very low. Due to these pharmacological properties the compounds of formula I according to the publications mentioned above and further references can be used as psycho-stimulating agents or as anti-depressive agents.
The prior known fields of use for the compounds of formula I accordingly was limited to diseases in which the brain falls ill causing disturbances of the intellect or mind, without (obligatory) influence on or degeneration of the motor nerves. As explained above, in ALS patients quite to the contrary the motor nerves become destroyed, but the intellect remains clear and the minds remain healthy and active. Therefore it was unforeseeable that the compounds of formula I or medicaments containing them, respectively, may cause improvements in the condition of ALS patients showing completely different symptoms in comparison to those shown by patients suffering from psychiatric disorders.